Naturally occurring amino acids include hydrolysis products of proteins and components of antibiotics and other microbiological metabolic products. These naturally occurring amino acids exist in enantiomeric forms. It has been found that a number of .alpha.-alkyl analogs when of the same enantiomeric configuration have the property of altering the metabolic path normally taken, producing results which are adaptable to being used to therapeutic advantage both directly as therapeutic agents and indirectly as agents for study of biological functions leading to means for therapeutic methods. Thus, for example, methyldopa, L-.alpha.-methyl-3,4-dihydroxyphenylalanine, inhibits the decarboxylation of dopa and 5-hydroxytryptophan, thereby decreasing the concentration of 5-hydroxytryptamine, dopamine and norepinephrine in the central nervous system. This metabolic behavior manifests itself, in a hypotensive effect which has been utilized therapeutically in a well-known antihypertensive drug, methyldopa. Other .alpha.-alkyl amino acids with the same enantiomeric configuration as those of the naturally occurring amino acids have been found also to be inhibitors of certain functions of amino acids and useful at the very least for the study of metabolic inhibition and metabolic pathways. Thus, L-(-)-.alpha.-methylphenylalanine has been reported to be tyrosine hydroxylase inhibitor (Bollinger, F. W., J. Med. Chem., 14, 373 (1971) and U.S. Pat. No. 3,758,559) and to have properties that make it more useful for treatment of heart condition than L-(-)-.alpha.-methyltyrosine because it has less of a tendency to cause drowsiness and mental depression. The preparation and utilization of .alpha.-methylphenylalanine for the synthesis of antimitotic peptides which may be ultimately useful for inhibition of cancerous tumor growth is reported in C.R. Acad. Sc. Paris, 268, 307. The resistance of peptides containing .alpha.-methylamino acids to the action of proteolytic enzymes are noted in F. Turk et al., Molecular Pharmacology, 12, 217-224 (1976). Thus, .alpha.-alkyl analogs of naturally occurring amino acids are of useful therapeutic and biological applications.
In all of the foregoing, the .alpha.-alkyl analog is in an enantiomeric configuration corresponding to that of the non-alkylated amino acid. The customary method for obtaining enantiomers has been to prepare the racemic compound and then to subject the racemic compound to resolution. A method which would permit entry of an alkyl group into an optically active .alpha.-amino acid to produce an .alpha.-alkyl amino acid of the same enantiomeric configuration, i.e., an enantioretentive process, would be highly desirable. In the literature, there has been reported a method for alkylating an enantiomer with retention of configuration which has been successful with proline but it has not been successful with the acyclic amino acids, i.e., amino acids in which the .alpha.-amino nitrogen is not part of a cyclic system. Since amino acids other than proline and hydroxyproline are acyclic at the .alpha.-amino position, there is still a need for a process whereby amino acids may be alkylated with retention of configuration when the amino acid is acyclic.